An example of a method known for producing an N-monoalkyl-3-hydroxy-3-(2-thienyl)propanamine is reducing 1-(2-thienyl)-3-chloropropane-1-one with sodium borohydride in ethanol to give 3-chloro-1-(2-thienyl)-1-propanol, halogen-exchanging this 3-chloro-1-(2-thienyl)-1-propanol with sodium iodide in acetone to give 3-iodo-1-(2-thienyl)-1-propanol, and reacting this 3-iodo-1-(2-thienyl)-1-propanol with an aqueous monomethylamine solution in tetrahydrofuran (CHIRALITY, 12, 26-29 (2000)). This method is not industrially advantageous since the starting material, i.e., 1-(2-thienyl)-3-chloropropane-1-one, is a highly unstable compound.
An example of a method known for producing N,N-dimethyl-3-hydroxy-3-(2-thienyl)propanamine is reacting 2-acetylthiophene with a dimethylamine hydrochloride in isopropanol in the presence of paraformaldehyde and hydrochloric acid to give 2-thienyl 2-dimethylaminoethyl ketone, and reducing this ketone with sodium borohydride in ethanol (Japanese Unexamined Patent Publication No. 1995-188065).
When an N-monoalkyl-3-hydroxy-3-(2-thienyl)propanamine is produced according to the method described immediately above using a monoalkylamine hydrochloride in place of a dimethylamine hydrochloride, it is problematic in that a dimeric N,N′,N″-alkyl-bis[1-[3-oxo-3-(2-thienyl)propane]]amine is generated due to the unstable production intermediate, i.e., 2-thienyl 2-monoalkylaminoethyl ketone, which results in a low yield of N-monoalkyl-3-hydroxy-3-(2-thienyl)propanamine obtained after the reduction with sodium borohydride.